• Biotherapeutics

    A year of advancing novel regenerative biotherapeutics toward patient care

Image of biomanufacturing

Mayo Clinic's Center for Regenerative Biotherapeutics has advanced the development and biomanufacturing of novel therapeutics, called biologics, for cancer and inflammatory conditions into clinical trials.

Image of Julie Allickson, Ph.D.
Julie Allickson, Ph.D.

"My dream has been to develop innovative technologies that go beyond treating symptoms to curing diseases. The ultimate aim is to ensure that these advancements are accessible to all patients in need," says Julie Allickson, Ph.D., the Michael S. and Mary Sue Shannon Director of the Mayo Clinic Center for Regenerative Biotherapeutics.

Dr. Allickson is also the Otto Bremer Trust Director, Biomanufacturing and Product Development, Center for Regenerative Biotherapeutics.

Biomanufacturing uses living organisms to manufacture medicines known as biologics that are made from human sources such as blood and cells. Biologics have shown potential for targeted healing with few side effects.

The biomanufacturing process is like a bridge that moves biologics from the lab into first-in-human clinical trials. From there, Mayo Clinic aims to license these technologies to industry collaborators who can conduct clinical trials and commercialize them, thereby making them accessible to patients worldwide.

"To ensure broad access to new medicines, the most effective approach is to bring them to market," says Dr. Allickson. "We are evaluating the scientific rigor required to scale up the production of new drugs. Additionally, we are establishing a streamlined process for advanced biomanufacturing that incorporates automation. Our goal is to transfer production of the medicines to companies capable of replicating our manufacturing process. This will enable them to advance the technology toward obtaining regulatory approval."

Groundbreaking treatments for cancer

The Center for Regenerative Biotherapeutics has reached several milestones in forwarding cutting edge cell therapies to early-stage clinical trials at Mayo Clinic, including:

Biomanufacturing a Mayo Clinic-developed chimeric antigen therapy (CAR-T cell therapy)

Chimeric antigen receptor-T cell therapy (CAR-T cell therapy) is a regenerative immunotherapy in which a patient's T cells are genetically modified to recognize and stop cancer. A new CAR-T cell therapy developed in the lab of Hong Qin, M.D., Ph.D., is aimed at B cell blood cancers that have returned and no longer respond to treatment. Mayo Clinic in Florida is preparing to biomanufacture this new cancer drug, known as BAFF-R, for a phase 1 clinical trial in early 2024. Dr. Qin is working on additional new CAR-T technologies for treating cancer.

"At Mayo Clinic we firmly believe that biomanufacturing CAR-T cell therapy on-site will expedite this lifesaving treatment to patients," says Dr. Allickson. "Backlogs can occur when cells are sent to an external manufacturer, causing delays that cancer patients can’t afford."

Biomanufacturing an experimental cell-based ovarian cancer vaccine. In this pioneering research led by Keith Knutson, Ph.D., and Matthew Block, M.D., Ph.D., white blood cells are extracted from blood, biomanufactured to become dendritic cells and returned to the patient. Dendritic cells act as crusaders that march through the body, triggering the immune system to halt disease progression. Manufacturing the cells at Mayo Clinic is critical so adjustments can be made for each patient's individual cancer.

New biomanufacturing facilities open

Mayo Clinic is expanding the number of Current Good Manufacturing Practice (CGMP) facilities needed to manufacture biologic therapies for clinical trials. CGMP facilities are clean rooms where therapeutic agents are manufactured in environments free of contamination and meet Food and Drug Administration specifications for safety, identity, strength, purity and quality.

Three new clean rooms opened recently in Florida. A new CGMP facility in One Discovery Square in Rochester, Minn., is ready to begin operations. Mayo Clinic in Arizona is taking an innovative approach of setting up CGMP clean rooms for 3D printing and 3D bioprinting. Mayo Clinic is among the first academic medical centers to 3D bioprint living cells, bones, or organs.

"What differentiates Mayo Clinic is its ability to 3D bioprint cells with CGMP bioprinters in a CGMP-compliant clean room," says Dr. Allickson. "This unique ability distinguishes us as a leader in this field for which we are gaining increasing recognition for our expertise."

A look ahead to 2024

The Center for Regenerative Biotherapeutics has advanced several cell-based therapies to the process and analytical development stage in preparation for biomanufacturing in 2024. Process development establishes standard operating procedures for manufacturing to ensure an experimental therapy is safe and of consistent quality for testing on humans in clinical trials.

Technologies in process development include:

Oncolytic virus for a two-pronged attack on cancer

The team of Richard Vile, Ph.D., is developing genetically engineered viruses with potential to not only destroy cancer, but also trigger an immune response for a second wave of cancer destruction. This technology, known as oncolytic virus, will be combined with CAR-T cell therapy to target solid tumors in patients with liver cancer.

Immune cells to address inflammatory conditions

Supported by a grant from the Skoll Foundation, researchers are studying immune cells to address inflammatory conditions. They are investigating whether these cells and their secretomes could be possible treatments for inflammatory conditions such as lupus and inflammatory bowel disease. Immune cells defend the body against infection. Secretomes are the healing properties released by cells.

CAR-T cell therapy targeting thyroid cancer, graft-versus-host disease and inflammatory bowel disease

Groundbreaking technology developed in the lab of Saad Kenderian, M.B., Ch.B., would expand CAR-T cell therapy beyond blood cancers to solid tumors. This discovery targets thyroid hormone stimulating receptor (TSHR) found on the surface of thyroid cancer tumors. Also in process development is a unique CAR-T cell therapy from Dr. Kenderian' s lab developed from mesenchymal stem cells. It will initially treat graft-versus-host disease, a rare complication from a bone marrow transplant, and inflammatory bowel disease.

Dr. Allickson sees an exciting year ahead that will include research and development of Regulatory T-cells, often called "Tregs."  Tregs play a critical role in regulating the immune system. They show potential for treatment of autoimmune diseases such as rheumatoid arthritis and colitis in which the body mistakenly attacks healthy cells.

"It's a privilege and an honor to be at Mayo Clinic where we can research and develop promising long-term or permanent solutions for patients with rare and complex disease," says Dr. Allickson.